Package assembly

ABSTRACT

A method and apparatus for packaging a medical device includes a package assembly that defines a multi-chambered interior. The interior chambers include a primary and a secondary chamber. A partition, which has a gas permeable vent, separates the primary chamber from the secondary chamber. The package is constructed from a variety of materials that provide the interior with a long term, low humidity, sterile environment.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.12/143,164, filed Jun. 22, 2008, the entire disclosures of which ishereby incorporated by reference.

BACKGROUND OF THE INVENTION

1 . Field of the Invention

In some embodiments this invention relates to a package assemblysuitable for use with environmentally sensitive products, and moreparticularly for use with one or more medical devices.

2. Description of the Related Art

Packages suitable for use with environmentally sensitive products suchas medical devices employ various configurations and/or mechanisms toprovide the package interior, and the medical device contained therein,with a secure and sterile storage environment. Modern medical deviceshowever, often employ a drug component that can complicate the packagingsolution by requiring more than just a sterile environment.

From providing moisture control, to physical protection, the addition ofa drug component, such as a coating, upon a medical device to bepackaged requires more dynamic packaging solutions than those presentlyavailable.

Some examples of known packaging solutions that are directed to medicaldevices include:

U.S. Pat. No. 5,577,368 to Hamilton et al. and U.S. Pat. No. 6,174,934to Sun et al. The packages and packaging procedures described in thesereferences seek to remove the oxygen/atmosphere from the packaging priorto radiation sterilization of medical implants made of polymericmaterial in order to reduce the wear resistance of the polymericimplant.

U.S. Pat. No. 4,941,308 to Grabenkort et al. discloses sterilizing theinterior of a package before placing the product in an inner package,sterilizing the product in the inner package, and then placing the innerpackage into an outer package. Grabenkort et al. uses ethylene oxide gas(EtO) for the sterilization.

U.S. Pat. No. 7,040,485 to Gupta and U.S. Publication 2007/0084144 A1 toLabrecque et al. describe pouches that employ gas permeable headersintended to allow transfer of gasses between the pouch interior and theheader before and during sterilization. These headers extend out fromthe pouch and may be optionally removed.

Despite the availability of such packaging solutions, there remains aneed for an efficient packaging assembly and method suitable for usewith particularly specialized products such as medical devices, andparticularly medical devices having a drug coating or similartherapeutic component.

The art referred to and/or described above is not intended to constitutean admission that any patent, publication or other information referredto herein is “prior art” with respect to this invention. In addition,this section should not be construed to mean that a search has been madeor that no other pertinent information as defined in 37 C.F.R. § 1.56(a)exists.

All US patents and applications and all other published documentsmentioned anywhere in this application are incorporated herein byreference in their entirety.

Without limiting the scope of the invention a brief summary of some ofthe claimed embodiments of the invention is set forth below. Additionaldetails of the summarized embodiments of the invention and/or additionalembodiments of the invention may be found in the Detailed Description ofthe Invention below.

A brief abstract of the technical disclosure in the specification isprovided as well only for the purposes of complying with 37 C.F.R. 1.72.The abstract is not intended to be used for interpreting the scope ofthe claims.

BRIEF SUMMARY OF THE INVENTION

In at least one embodiment, the invention is directed to a packageassembly constructed from a gas impermeable shell or walls that definethe package interior. The interior is divided into chambers by apartition. The partition defines a vent of at least one gas permeablematerial. In some embodiments the vent allows gas to flow only from aprimary chamber (a product containment chamber) to an adjacent,secondary chamber (which may contain or include a desiccant or moistureabsorbing substance).

The interior comprises two or more chambers as desired. The chambers ofthe assembly are separately accessible and can be individually sealed toallow one chamber (and/or its contents) to be manipulated withoutcompromising the sterile environment of the adjacent chamber.

In some embodiments the outer shell of the assembly is characterized hashaving first (i.e., front) and second (i.e., back) walls. The walls maybe of identical or significantly different construction, and may includea variety of materials and characteristics in their construction. Forexample, in some embodiments the package assembly comprises a UV barrierin the make-up of one wall while such a barrier may be considered anunnecessary expense on the opposing wall. Depending on the nature of theproduct to be contained in the assembly, the environment where it is tobe stored, etc., embodiments of the invention will include walls havingone or more layers of material to provide at least one oxygen barrierlayer, at least one puncture resistant layer, at least one moisturevapor barrier layer, at least one ultraviolet barrier layer, and anycombination thereof.

In at least one embodiment the vent is positioned in an opening of apartition wall. The partition wall is constructed of one or more polymermaterials that define the vent opening. The vent can be constructed outof a variety of gas permeable materials, and may include materials suchas TYVEK®. In some embodiments the vent includes one or more valvemechanisms, (e.g. perforation(s), diaphragm(s), degassing valve(s),etc.) to provide the vent with a one-way direction of potential gasflow.

As indicated above, one of the chambers of the assembly is configured tocontain a desiccant. The desiccant can be of any desired configurationand include any known moisture absorber and/or oxygen scavenger. Also asindicated above, one of the chambers is configured to contain a productsuch as a medical device. Embodiments of the present invention areparticularly suited for the long term stable containment of medicaldevices that employ one or more therapeutic agents (i.e., drug(s),etc.). Examples of such medical devices include drug eluting stentsand/or the delivery systems (catheters, etc.) upon which they aremounted.

In some embodiments the assembly is configured to provide a relativelylow humidity environment (relative humidity (RH) of about 5 percent orless) for at least one month. In some embodiments the low humidityenvironment is maintained for at least 18 months.

In addition to providing a unique package assembly having the featuresdescribed thus far, some embodiments of the present invention are alsodirected to packaging processes and methods.

These and other embodiments which characterize the invention are pointedout with particularity in the claims annexed hereto and forming a parthereof. However, for further understanding of the invention, itsadvantages and objectives obtained by its use, reference should be madeto the drawings which form a further part hereof and the accompanyingdescriptive matter, in which there is illustrated and described aembodiments of the invention.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)

A detailed description of the invention is hereafter described withspecific reference being made to the drawings.

FIG. 1 is a perspective view of an embodiment of the invention includingthe package assembly with a product contained therein and desiccantdepicted externally.

FIG. 2 is a lateral cross-sectional view of the embodiment of FIG. 1.

FIG. 3 is a longitudinal cross-sectional view of the embodiment of FIG.1 wherein the partition structure is illustrated.

FIG. 4 is a close-up view of an embodiment of the partition shown inFIGS. 2 and 3.

FIG. 5 is a longitudinal cross-sectional view of an embodiment whereinthe header region includes a gas permeable header.

FIG. 6 is a line graph showing the relative humidity of the assemblyinterior over time.

FIG. 7 is a block diagram depicting the steps of a packaging process.

DETAILED DESCRIPTION OF THE INVENTION

While this invention may be embodied in many different forms, there aredescribed in detail herein specific preferred embodiments of theinvention. This description is an exemplification of the principles ofthe invention and is not intended to limit the invention to theparticular embodiments illustrated.

For the purposes of this disclosure, like reference numerals in thefigures shall refer to like features unless otherwise indicated.

As described above, various embodiments of the present invention aredirected to package assemblies. An example of a package assembly 10 isshown in FIG. 1. In some embodiments the assembly 10 is particularlysuited for use in the packaging of medical devices, particularly thoseincorporating a therapeutic agent or drug component. Such medicaldevices may be of any type, and include implantable medical devices suchas stents, and/or the catheters or other delivery systems used to deploythem.

An example of such a medical device product 100 is shown positioned inthe interior 12 of a primary chamber 14 of the assembly 10. The interior12 of assembly 10 also includes a secondary chamber 16, which can beconfigured to house at least one desiccant 110 (shown externally).

Desiccant 110 can be of any type or configuration known, including butnot limited to: silica gel, clay, molecular sieves, potassiumpermanganate, activated carbon and activated alumina. Examples of oxygenand/or moisture scavengers that may comprise or be incorporated into thedesiccant include but are not limited to: calcium oxide, iron oxidepowders, sulfites, bisulfites, butylated hydroxytoluene (BHT), butylatedhydroxyanisole (BHA), oxygen absorbable polymers, etc.

The division of the package interior 12 into a primary chamber 14 and asecondary chamber 16 is best shown in FIG. 2. As shown, each chamber isdefined on its outer perimeter by a wall 24 and 26. Walls 24 and 26 canbe of the same materials and/or construction, or distinctly different,depending on a variety of factors that will be discussed in greaterdetail below. The inner perimeter of each chamber 14 and 16 is definedby a partition 28.

Prior to the closing and sealing of the chambers 14 and 16, each chamberis provided with respective opening 40 a and 40 b. Openings 40 a and 40b can be of any type or mechanism desired. In the embodiment shown inFIGS. 1-2, each of the walls 24 and 26 and partition 28 havecorresponding sealed or closed borders 42 that are sealed togetherduring the manufacture of the assembly 10. In the depicted embodimentopening 40 a is provided into the primary chamber 14 and defined by thecorresponding unsealed or open borders 44 (FIG. 1) of the wall 24 and ofthe partition 28. Opening 40 a is closed by sealing the open borders 44of wall 24 and partition 28 together. Similarly, opening 40 b isprovided into the secondary chamber 16 and defined by the correspondingunsealed or open borders 46 (FIG. 1 only) of the wall 26 and of thepartition 28. Opening 40 b is closed by sealing the open borders 46 ofwall 26 and partition 28 together.

The closing and sealing of openings 40 a and 40 b can be by mechanicalengagement, adhesive engagement, by application of a heat seal, etc. Insome embodiments opening 40 b is capable of being easily and repeatedlybeing opened and resealed.

In at least one embodiment, an example of which is shown in FIG. 5, theassembly 10 includes a header 41 which includes one or more ventedregion (see vent 32) similar to that discussed below in regard to thepartition 28. The header 41 is a region of the assembly 10 adjacent tothe chambers 14 and/or 16. The header 41 can include the region of theassembly defining the openings 40 a and/or 40 b or be positioned on theopposing end of the assembly 10 such as in the manner shown. The header41 can be entirely or partially constructed of a gas permeable materialsuch as, for example, TYVEK® thereby allowing increased Ethylene Oxide(EtO) ingress during sterilization of the package assembly 10.Sterilization processes involving the assembly 10 are discussed ingreater detail below.

In some embodiments the shape and arrangement of the walls 24 and 26,and the partition 28 can be arranged such that more than one border of agiven wall and/or the partition defines the openings 40 a and 40 b.

Walls 24 and 26 are constructed from at least one layer of polymermaterial(s), such as for example: polyethylene, which allow the adjacentwalls 24 and 26 to be engaged and sealed to one another as well as tothe material of the partition 28.

Walls 24 and 26 can be supplemented with a variety of additionalmaterial layers (via co-extrusion, lamination, etc.), wherein each layeris selected for desired performance characteristics. For example,embodiments of the invention will include walls 24 and/or 26 having atleast one oxygen barrier layer, at least one puncture/tear resistantlayer, at least one moisture vapor barrier layer, at least oneultraviolet barrier layer, and any combination thereof

Some non-limiting examples of materials that provide a desiredcharacteristic are represented as follows:

-   -   Oxygen barrier layer: Ethylene-vinyl alcohol copolymer (EVOH),        polyvinylidenechloride (PVDC), foil, metalized polyethylene        terephthalate (PET)/biaxially oriented nylon (BON), aluminum        oxide coatings, silica oxide coatings, polyvinyl alcohol (PVOH),        TOP AS®, and any combinations thereof.    -   Puncture/Tear resistant layer: BON, bi-axially oriented        polypropylene (BOPP), bi-axially oriented polyester (BOPET),        linear low-density polyethylene (LLDPE), Ultra Low Density        Polyethylene (ULDPE), TYVEK® and any combinations thereof.    -   Moisture vapor barrier layer: metalized polypropene        (PP)/PET/BON, aluminum oxide coated polymers, silica oxide        coated polymers, ALCAR®-flourocarbons, and any combinations        thereof.    -   UV barrier layer: foil, metalized PP/PET/BON, polymers with UV        blockers.

The particular combination of materials and/or layers of materials inthe formation of walls 24 and 26 is tailored to specific packagingrequirements of the device to be packaged, the storage environment ofthe assembly 10, etc. Multiple layers of similar or dissimilarmaterials, the relative thickness selected for each layer of material,etc., can be modified as desired in order to vary the characteristicproperties of the individual materials, the structure of the walls 24and/or 26, and thus, the performance of the assembly 10 itself.

In at least one embodiment, the partition 28 comprises at least onesterile, gas permeable or breathable, material(s). In some embodiments,an example of which is shown in FIG. 3 in order to improve the sealbetween walls 24 and 26 to the partition 28, the partition 28 comprisesa housing or housing material 30 that defines an opening 32therethrough. The housing material 30 may be any type of materialselected for flexibility and ease in bonding or sealing with thematerial of the walls 24 and 26. Some examples of suitable materialsinclude: LLDPE, Nylon, TYVEK®, Foil, etc.

Secured to the housing material 30 across the opening 32 is positioned avent 34 which is constructed of the previously mentioned gas permeablematerial(s).

Vent 34 is configured to allow gases to pass from the primary chamber 14into the secondary chamber 16 both during the packaging process andthroughout the shelf-life of the assembly 10. In some embodiments thevent 34 is configured to allow gases as well as moisture to pass in onlyone direction from the primary chamber 14 and into the secondary chamber16. While the presence of the desiccant 110, such as is illustrated inFIG. 2, within chamber 16 will facilitate this pathway, vent 34 can alsobe configured to include a valve, diaphragm or other mechanism toprevent gas or moisture from reentering chamber 14.

One non limiting example of a degassing valve mechanism suitable for usein partition 38 is described in U.S. Pat. No. 7,178,555 the entirecontents of whish is incorporated herein by reference. In at least oneembodiment, an example of which is shown in FIG. 4, the partition 28includes at least one ingress valve 35 and at least one egress valve 37.Another example of a valve mechanism for use in partition 28 includesfilm and/or tape membranes fabricated on the partition and which overlaypores, slits, holes or other openings through the partition. Other typesand configuration of valve mechanisms can alternatively or additionallybe incorporated into the partition 28.

In some embodiments the vent has a minimum surface area of about 1square inch (6.45 cm²). In at least one embodiment the vent has asurface area of at least 9 square inches (58 cm²).

Some examples of sterile, breathable materials that the vent 34 can beconstructed from include but are not limited to: medical grade paper,micro-perforated polymer film or films, micro-perforated foil or foils,etc. More specific examples of materials include, but are not limitedto: polyethylene, polystyrene, polypropylene, high density polyethylene(HDPE), etc. In at least one embodiment the vent is constructed from aTYVEK®.

With the ability to customize and configure the material composition ofthe walls 24 and 26, as well as the construction of the partition 28 inmind, an example embodiment of the assembly 10, such as is illustratedin FIG. 2, and which is particularly suited for use with a drug coatedmedical device is described as follows:

EXAMPLE 1

Layer Material Approx. Thickness (mil) Walls 24 and 26 constructed of:LDPE-EVA (peelable interior) 2 LDPE 0.75 BON 0.60 LDPE 0.75 Foil 0.70White LDPE 1 PET (exterior) 0.48 Partition housing material 30constructed of: LLDPE 1.6 Nylon 0.8 LLDPE 1.6 Vent 34 is constructed ofTYVEK ®

In the above example, the various properties that the materials of walls24 and 26 exhibit, as well as the functional aspect of the partition 28and desiccant 110; provide a near optimum environment for minimizingpotential degradation of a therapeutic coating that a medical device 110includes. By providing the package assembly interior with total or neartotal UV protection, optimum moisture protection, and a sterile, sealedenvironment, the shelf-life of drugs and/or their respective polymermatrices can be maintained for extended periods of time.

For example, as illustrated by the chart of FIG. 6, followingsterilization and the final sealing of the package assembly, therelative humidity of the primary chamber 14, as well as the secondarychamber 16, is maintained at less than 5% for a duration of at least 1month. While the example illustrated in FIG. 6 is merely onerepresentative example of the initial performance characteristics ofassembly 10 in maintaining a low moisture environment for the short term(about 1 month depicted), in some embodiments similar performance of theassembly 10 is maintained for periods up to and exceeding 18 months.

It should also be noted that FIG. 6 illustrates that shortly after finalsealing of the package (approximately 70 hours) the actual relativehumidity maintained within the package interior can drop to as low asabout 3 percent to about 2 percent over the long term.

Providing a sealed and relatively low humidity environment is a clearbenefit to numerous sensitive compositions, such as many of thetherapeutic agents utilized with implantable medical devices. Someexamples of therapeutic agents that benefit from storage in assembly 10include but are not limited to the following drugs: Paclitaxel,Evorolimus, Sirolimus, etc. Similarly, polymer matrix materials that areoften utilized for the elution of such drugs from a medical device willbenefit from the internal environment of assembly 10. Non-limitingexamples of such matrix materials include but are not limited to:poly(lactic-co-glycolic acid) (PLGA), Polylactic Acid (PLA),Poly(styrene-b-isobutylene-b-styrene) (SIBS), Poly(dioxanone);poly(trimethylene); poly(caprolactone); polyanhidrides; polyphosphozene;etc.

When used to package an environmentally sensitive product, the insertionof the product into the assembly 10 is but one step in a variety ofpossible packaging methods or processes.

For example, in block diagram depicted in FIG. 7, a process forpackaging a medical device is depicted.

Such a process includes the initial step of a pre-sterile sealrepresented at block 50 wherein the medical device 100 is inserted intothe primary chamber 14 of the assembly 10 (shown in FIGS. 1-2) and thenthe chamber 14 is sealed in the manner previously described. As will bemade clear below, step 50 need not be undertaken in a sterileenvironment, though it can be if desired.

As represented by block 52 once chamber 14 is sealed, secondary chamber16 remains open and the entire assembly along with the product containedtherein is sterilized. The sterilization process may be in accordancewith any known sterilization technique, in accordance with thelimitations of the product. For example, the assembly can be subjectedto e-beam sterilization, Ethylene Oxide (EtO) sterilization, etc.

Depending on the sterilization process utilized, following sterilizationthe assembly is subjected to vacuum drying as represented by block 54.

As represented by block 56, following the sterilization procedure 52,and optional drying 54, the desiccant 110 is inserted into the secondarychamber 16 (shown in FIGS. 1-2).

Once the desiccant is in position within the secondary chamber the finalseal, represented by block 58, is applied to the opening 40 b of chamber16. In some embodiments final seal of the assembly includes theadditional steps of applying vacuum to the assembly and/or flushing theassembly interior with an inert gas before the opening of the secondarychamber is sealed.

It is recognized that maintenance of a sterile environment during theentire sealing process is important, particularly where the product inquestion is an implantable medical device. In some embodiments, theassembly is transferred or kept in a nitrogen cart between the steps ofthe packaging process described above.

Once the assembly is finally sealed, a label 112 can be applied to theassembly exterior (as depicted in FIG. 1) and the assembly is then boxedfor shipment as represented by block 60.

This completes the description of representative embodiments of theinvention. Those skilled in the art may recognize other equivalents tothe specific embodiment described herein which equivalents are intendedto be encompassed by the claims attached hereto.

The above disclosure is intended to be illustrative and not exhaustive.This description will suggest many variations and alternatives to one ofordinary skill in this art. The various elements shown in the individualfigures and described above may be combined or modified for combinationas desired. All these alternatives and variations are intended to beincluded within the scope of the claims where the term “comprising”means “including, but not limited to”.

Further, the particular features presented in the dependent claims canbe combined with each other in other manners within the scope of theinvention such that the invention should be recognized as alsospecifically directed to other embodiments having any other possiblecombination of the features of the dependent claims.

1. A dual compartment pouch comprising: front and back sheets of aflexible barrier film arranged in opposing face-to-face relation, eachhaving an inner surface, a top edge, a bottom edge, and opposite sideedges extending longitudinally from said top edge to said bottom edge;an inner sheet of a flexible barrier film disposed between the front andback sheets and having a top edge, a bottom edge, and opposite sideedges, the inner sheet defining first and second compartments within thepouch; side seams extending longitudinally along said opposite sideedges and joining the front and back sheets to the inner sheet; a bottomseam extending transversely along said bottom edges and joining thefront and back sheets to the inner sheet; an opening formed in the innersheet and providing communication between the first and secondcompartments; a breathable membrane disposed on the inner sheet andcovering said opening, said breathable membrane having a peripheral edgeoverlying the inner sheet and spaced from said side seams and bottomseam, the breathable membrane comprising a moisture vapor permeable,water-impermeable sheet material; and a seam located at or adjacent theperipheral edge of the breathable membrane joining the membrane to theinner sheet.
 2. The pouch of claim 1, wherein the breathable membranecomprises paper or a nonwoven fabric.
 3. The pouch of claim 1, whereinthe barrier film of the inner sheet includes a heat sealablethermoplastic material.
 4. The pouch of claim 1, wherein the top edge ofthe inner sheet is unconnected to the front sheet or the back sheet todefine access openings into the first and second compartments.
 5. Thepouch of claim 1, further comprising a frangible seal disposed betweenthe front sheet and the inner sheet towards a bottom end of the pouch.6. The pouch of claim 5, wherein the frangible seal has a chevron shapewith an apex directed towards the bottom edges of the back and innersheets.
 7. The pouch of claim 1, wherein the breathable membrane has asurface area of at least about 1 square inch.
 8. The pouch of claim 1,wherein the breathable membrane has a surface area of at least about 9square inches.
 9. The pouch of claim 1, wherein the top edges of theinner sheet and the back sheet extend beyond the top edge of the frontsheet.
 10. The pouch of claim 1, wherein the opening in the inner sheetand the breathable membrane are circular, and are joined to each otherby a continuous seam that is located at or adjacent the peripheral edgeof the breathable membrane.
 11. A sterilizable dual compartment pouchcomprising: front and back sheets of a flexible barrier film arranged inopposing face-to-face relation, each having an inner surface, a topedge, a bottom edge, and opposite side edges extending longitudinallyfrom said top edge to said bottom edge; an inner sheet of a flexiblebarrier film disposed between the front and back sheets and having a topedge, a bottom edge, and opposite side edges, the inner sheet definingfirst and second compartments within the pouch; side seams extendinglongitudinally along said opposite side edges and joining the front andback sheets to the inner sheet; a bottom seam extending transverselyalong said bottom edges and joining the front and back sheets to theinner sheet; a top seam extending transversely along said top edges andjoining the front and back sheets to the inner sheet and an openingformed in the inner sheet and providing communication between the firstand second compartments; a breathable membrane disposed on the innersheet and covering said opening, said breathable membrane having aperipheral edge overlying the inner sheet and spaced from said sideseams, top seam, and bottom seam, the breathable membrane comprising amoisture vapor permeable, water-impermeable sheet material; and acontinuous seam located at or adjacent the peripheral edge of thebreathable membrane joining the membrane to the inner sheet.
 12. Thesterilizable dual compartment pouch of claim 11, further comprising amedical device disposed in the second compartment.
 13. The sterilizabledual compartment pouch of claim 12, wherein the medical device is astent that is coated with a therapeutic drug agent.
 14. The sterilizabledual compartment pouch of claim 11, further comprising one or more of adesiccant or scavenging agent disposed in the first compartment.
 15. Amethod of sterilizing an article comprising providing the pouch of claim1; introducing an article into the second compartment; sealing the topedges of the inner sheet and the back sheet to each other; introducing asterilizing gas into the first compartment; passing the sterilizing gasfrom the first compartment to the second compartment via the breathablemembrane; introducing one or more absorbents into the first compartment;and sealing the top edge of the front sheet to the inner sheet.
 16. Themethod of claim 15, further comprising the step of flushing the firstand second compartments with an inert gas prior to the introduction ofone or more absorbents.
 17. The method of claim 15, wherein the articleis a stent that is coated with a therapeutic drug agent.
 18. The methodof claim 15, wherein the breathable membrane comprises paper or anonwoven.